Super‐Resolution Ultrasound Based Cell Tracking With Polymeric Nanobubbles
Abstract
ABSTRACT Tracking the fate of transplanted cells in vivo remains a major challenge for the development and monitoring of cell‐based therapies. Here, we report a nanobubble (NB) based acoustic labeling strategy that enables ultrasound localization microscopy (ULM) to track transplanted cells in tumors with single‐cell‐scale sensitivity and super‐resolution spatial precision. We developed stable, biocompatible poly(butyl cyanoacrylate) NB that are efficiently internalized by cells and generate strong intracellular ultrasound signals. Furthermore, ULM allows the real‐time visualization of individual cells, their localization, and trajectory reconstruction in flow phantoms and murine breast cancers. In the latter, NB‐labeled bone marrow‐derived mononuclear cells were tracked in vivo following intra‐arterial injection, whereas unlabeled cells remained undetectable. By integrating cell trajectories with microbubble‐based super‐resolution vascular maps, our approach allows identification of the blood vessels that delivered the cells. This clinically compatible imaging strategy expands the application of ULM beyond vascular mapping and provides a platform for high‐resolution, dynamic monitoring of cell‐based therapies.
Article Details
Authors (20)
Junlin Chen
Westlake University , , 600 Dunyu Road , ,
Xiaoyu Wang
Jilin Fan
Bi Wang
Institute For Experimental Molecular Imaging RWTH Aachen University Aachen Germany
Hanghang Fang
Institute For Experimental Molecular Imaging RWTH Aachen University Aachen Germany
Yurui Wang
Hao Cui
Mohammad Roufarshbaf
Institute For Experimental Molecular Imaging RWTH Aachen University Aachen Germany
Ekaterina Savina
Institute For Experimental Molecular Imaging RWTH Aachen University Aachen Germany
Alexandra Valeske
Institute For Experimental Molecular Imaging RWTH Aachen University Aachen Germany
Quim Peña
Institute For Experimental Molecular Imaging RWTH Aachen University Aachen Germany
Yang Shi
Andreas Herrmann
Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, Worringerweg 2, 52074 Aachen, Germany
Twan Lammers
Institute for Experimental Molecular Imaging
Mathias Hornef
Institute of Medical Microbiology Rheinisch‐Westfälische Technische Hochschule Aachen University Hospital Aachen Germany
Roman Barmin
Institute For Experimental Molecular Imaging RWTH Aachen University Aachen Germany
Thomas Lisson
Chair for Medical Engineering Ruhr University Bochum Bochum Germany
Georg Schmitz
Chair for Medical Engineering Ruhr University Bochum Bochum Germany
Anne Rix
Institute For Experimental Molecular Imaging RWTH Aachen University Aachen Germany
Fabian Kiessling
Institute for Experimental Molecular Imaging, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital